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Research Article

Self-targeting visualizable hyaluronate nanogel for synchronized intracellular release of doxorubicin and cisplatin in combating multidrug-resistant breast cancer

Wen Ma1,§, Qiling Chen1,§, Weiguo Xu2,§, Meng Yu1, Yuanyuan Yang1, Binhua Zou1, Yu Shrike Zhang3( ), Jianxun Ding2( ), Zhiqiang Yu1 ( )
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge MA 02139, USA

§ Wen Ma, Qiling Chen, and Weiguo Xu contributed equally to this work.

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Graphical Abstract

Abstract

Multidrug-resistance (MDR) featuring complicated and poorly defined mechanisms is a major obstacle to the success of cancer chemotherapy in the clinic. Compound nanoparticles comprising multiple cytostatics with different mechanisms of action are commonly developed to tackle the multifaceted nature of clinical MDR. However, the different pharmacokinetics and release profiles of various drugs result in inconsistent drug internalization and suboptimal drug synergy at the tumor sites. In the present study, a type of self-targeting hyaluronate (HA) nanogels (CDDPHANG/DOX) to reverse drug resistance through the synchronized pharmacokinetics, intratumoral distribution, and intracellular release of topoisomerase II inhibitor doxorubicin (DOX) and DNA- crosslinking agent cisplatin (CDDP) is developed. With prolonged circulation time and enhanced intratumoral accumulation in vivo, CDDPHANG/DOX shows efficient drug delivery into the drug-resistant MCF-7/ADR breast cancer cells and enhanced antitumor activity. Besides, fluorescence imaging of DOX combined with the micro-computed tomography (micro-CT) imaging of CDDP facilitates the visualization of this combination tumor chemotherapy. With visualizable synchronized drug delivery, the self-targeting in situ crosslinked nanoplatform may hold good potential in future clinical therapy of advanced cancers.

Keywords

hyaluronate nanogelself-targetabilityintracellular drug codeliverymultimodal imagingreversal of multidrug resistance

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Nano Research
Volume 14 Issue 3,
March 2021
Pages 846-857
DOI: 10.1007/s12274-020-3124-y
Cite this article:
Ma W, Chen Q, Xu W, et al. Self-targeting visualizable hyaluronate nanogel for synchronized intracellular release of doxorubicin and cisplatin in combating multidrug-resistant breast cancer. Nano Research, 2021, 14(3): 846-857. https://doi.org/10.1007/s12274-020-3124-y
Topics:
Chemotherapy Controlled drug deliveryDiseasesFluorescence imagingNanostructured materialsTumors

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Received: 19 July 2020
Revised: 09 September 2020
Accepted: 12 September 2020
Published: 01 March 2021
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature
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